CORE 2 ? SUMMARY The Biospecimen Core (Core 2) will play a central role by providing pathology and biospecimens support, and appropriate infrastructure to the P01. Its expertise in pathology, molecular biology, and molecular epidemiology will contribute to the validity of the proposed study as it will provide centralized histopathologic review and the correct diagnosis of all tumor samples, and ensure utilization of the appropriate tissue. This core will provide a systematic co-extraction of DNA and RNA from unique tumor cell lysates which will ensure proper integration of findings across different research aims and add to the validity of the P01 results. The core will also conduct a systematic quality assessment of samples and derived data to ensure experimental success of the individual research projects. This core will distribute specimens to Program Projects 1-3, and related data to Core 1 where it will be made available to all projects and cores. The core will utilize the MSK Institutional Pathology Core and Clinical Research Database (CRDB). The latter will help centralize the repository of data and provide an integrated specimen tracking system. The Biospecimen Core will be led by Dr. Klaus Busam, leader of Dermatopathology at MSK. He is recognized for his experience with melanoma diagnostic issues and has extensive experience in managing archival and frozen tissue samples. He will lead the diagnostic aspects of the project, and will ensure the utilization of high quality banked melanomas through assessment of cell heterogeneity and purity. Dr. Orlow will be the co-leader of the Biospecimen Core. She directs the Molecular Epidemiology Laboratory at MSK and has a wealth of experience in the handling and testing of different types of tissues, and in the banking and distribution of specimens for various hospital based and large multicenter epidemiologic studies. She will oversee and coordinate the collection, processing, and testing of specimens, data entry, and re-distribution of specimens and data for the P01. Drs. Busam and Orlow are co-Principal Investigators of the Institutional Melanoma Disease Management Team. They have collaborated with the overall leaders and several investigators of this Program Project for many years. Together, they will oversee the administrative aspects of the core. The objectives of the Biospecimen Core (Core 2) are to: (1) assemble the collection of specimens and establish relevant histopathologic, immunohistochemical and molecular data relevant to the investigation of melanoma tumors and host genetics; (2) provide expert review of melanoma tumors with documentation of tumor diagnosis, histopathologic prognostic features, volume, viability and purity of available tumor issue; (3) perform systematic extraction and characterization of nucleic acids; (4) provide RNA and DNA sample sets and associate sample annotation as needed to the individual research projects. As part of this objective, the Biospecimen Core will procure specimens for mutational testing with the MSK-IMPACTTM assay and digital PCR.